Phase I trial combining pembrolizumab and doxorubicin in patients with metastatic triple negative breast cancer.

Abstract

e13071 Background: Pembrolizumab (pembro) in combination with chemotherapy (chemo) has recently become standard of care in patients with programmed death-ligand 1 (PD-L1) positive metastatic triple negative breast cancer (mTNBC). Optimal chemo partner with pembro remains debatable. The current phase I study evaluated the safety and efficacy of doxorubicin (dox) + pembro in anthracycline-naïve mTNBC patients (NCT02648477). Methods: Patients with mTNBC, no prior anthracycline, and ≤2 lines of prior chemo for metastatic disease were enrolled. Patients received pembro 200mg IV and 50-60 mg/m2 dox IV every 3 weeks x6, followed by pembro maintenance until progression or unacceptable toxicity. The primary objectives were safety and objective response rate (ORR per RECIST 1.1). For the safety lead-in, we employed a 3-at-risk rolling design. Results: Ten patients were accrued between March 2016 and November 2019. The trial stopped early due to poor accrual. The first 3 patients received dox at 50mg/m2 without dose limiting toxicities and dose was escalated to 60mg/m2 for the remaining patients. Median age was 62 years (range 41-87). Grade ≥ 3 AEs were: 4 neutropenia, 2 dyspnea, 2 fatigue, 1 oral mucositis, 1 hyponatremia, 1 acidosis, 1 alkalosis, 1 hypotension and 1 respiratory failure. One patient (age 87) received 1 dose of therapy, developed neutropenia and respiratory failure which led to death, and was not eligible for response assessment. 1 patient did not have RECIST measurable disease. Two patients had dose delay (1 G3 neutropenia and 1 G2 upper airway infection). 1 patient had dose reduction due to G3 fatigue. Immune toxicity was consistent with known pembro toxicity. Of 9 evaluable patients, responses were : 1 CR, 3 PR, 2 UPR, 2 SD and 1 PD, which translated to a best ORR of 67% (95% CI, 13.7%, 78.8%). CBR at 6 mo was 56% (95% CI 21.2%, 86.3%). Median follow-up time was 34.6 mo (range 14.5 - 45.4 mo). Median PFS was 5.2 mo (95% CI 4.7, NA); and median OS was 15.6 mo (95% CI 13.3, NA). Eight patients had PD-L1 (22C3) testing: 4 positive and 4 negative. No association between the PD-L1 status and response was observed. Conclusions: The combination of pembro+dox was well tolerated and had modest activity in anthracycline-naïve patients with mTNBC. The finding needs to be further confirmed with future study. Clinical trial information: NCT02648477.